The present invention relates to nucleic acids of the general formula (I): (N.sub.uG.sub.lX.sub.mG.sub.nN.sub.v).sub.a and derivatives thereof as an immunostimulating agent/adjuvant and to compositions containing same, optionally comprising an additional adjuvant. The present invention furthermore relates to a pharmaceutical composition or to a vaccine, each containing nucleic acids of formula (I) above and/or derivatives thereof as an immunostimulating agent, and optionally at least one additional pharmaceutically active component, e.g. an antigenic agent. The present invention relates likewise to the use of the pharmaceutical composition or of the vaccine for the treatment of cancer diseases, infectious diseases, allergies and autoimmune diseases etc. Likewise, the present invention includes the use of nucleic acids of the general formula (I): (N.sub.uG.sub.lX.sub.mG.sub.nN.sub.v).sub.a and/or derivatives thereof for the preparation of a pharmaceutical composition for the treatment of such diseases.

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of APP RNA in a cell or animal, and in certain instances reducing the amount of APP protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurodegenerative disease or disorder. Such symptoms and hallmarks include cognitive impairment, including a decline in memory and language skills, behavioral and psychological symptoms such as apathy and lack of motivation, gait disturbances and seizures, progressive dementia, and abnormal amyloid deposits.

Therapeutic oligonucleotides comprising pharmacokinetic (PK)-modifying anchors are provided. Methods for treating diseases or disorders comprising administering to a subject a therapeutic oligonucleotide comprising one or more PK-modifying anchors are provided.

Disclosed herein are glutathione-sensitive oligonucleotides and methods of using the same. Any oligonucleotide of interest may be modified with a glutathione-sensitive moiety, including oligonucleotides used for in vivo delivery, such as nucleic acid inhibitor molecules. Typically, the glutathione-sensitive moiety is used to reversibly modify the 2′-carbon of a sugar moiety in one or more nucleotides in the oligonucleotide, although other carbon positions may also be modified with the glutathione-sensitive moiety. Also disclosed are glutathione-sensitive nucleotide and nucleoside monomers, including glutathione-sensitive nucleoside phosphoramidites that can be used, for example, in standard oligonucleotide synthesis methods. In addition, glutathione-sensitive nucleotide and nucleoside monomers without a phosphoramidite can be used therapeutically, for example, as anti-viral agents.

The present disclosure includes the use of a miRNA inhibitor for treating a tauopathy associated with a decreased level of SIRT1 protein or SIRT1 gene expression, PGC-1α protein and/or PGC-α gene expression, and/or CD36 and/or CD36 gene expression.

The present specification provides a drug that causes highly-efficient skipping of exon 51 in the human dystrophin gene. The present specification provides an antisense oligomer having an activity to induce skipping of exon 51 in the human dystrophin gene.

Improved compositions and methods for treating a disease or disorder through target exon skipping, and preferably muscular dystrophy by administering antisense thiomorpholino molecules capable of binding to a selected target site in the human dystrophin gene to induce exon skipping to produce a functional Dystrophin protein.

The present disclosure includes the use of a miRNA inhibitor for treating a disease or condition associated with a decreased level of SIRT1, PGC-1α, CD36, LRRK2, NRG1, STMN2, VLDLR, NRXN1, GRIA4, NXPH1, PSD-95, and/or synaptophysin protein or SIRT1, PGC-1α, CD36, LRRK2, NRG1, STMN2, VLDLR, NRXN1, GRIA4, NXPH1, PSD-95, and/or synaptophysin gene expression. In some aspects, the miRNA inhibitor can be used to treat a disease or condition associated with an increased level of caspase-3 protein or gene expression. The miRNA inhibitor useful for the present disclosure can inhibit miR-485 expression and/or activity, which in turn can increase the level of SIRT1, PGC-1α, CD36, LRRK2, NRG1, STMN2, VLDLR, NRXN1, GRIA4, NXPH1, PSD-95, and/or synaptophysin protein or gene expression; and/or can decrease the level of caspase 3 protein or gene expression.

Provided herein are processes for preparing an oligomer (e.g., a morpholino oligomer). The synthetic processes described herein may be advantageous to scaling up oligomer synthesis while maintaining overall yield and purity of a synthesized oligomer.

The present invention relates to a COPS3 inhibitor for use in treatment of an HBV infection, in particular a chronic HBV infection. The invention in particular relates to the use of COPS3 inhibitors for destabilizing cccDNA, such as HBV cccDNA. The invention also relates to nucleic acid molecules which are complementary to COPS3 and capable of reducing the level of a COPS3 mRNA. Also comprised in the present invention is a pharmaceutical composition and its use in the treatment of a HBV infection.